Repeated generalized audiogenic seizures induce plastic changes on acoustically evoked neuronal firing in the amygdala.

Repetition of audiogenic seizures (AGS) (AGS kindling) results in increases in the duration of convulsive behavior and the emergence of cortical epileptiform EEG activity. These changes involve expansion of the neuronal network subserving these seizures. The amygdala (AMG) is postulated to become involved in this expanded network, but the neurophysiological basis of this process is unknown. The present study examined changes in chronically-recorded extracellular neuronal firing patterns in the lateral nucleus of AMG (LAMG) induced by AGS kindling in behaving genetically epilepsy-prone rats (GEPR-9s). Before AGS kindling, onset-only (36.1%), onset-delayed (50%) and delayed-only (13.9%) patterns of response to acoustic stimuli were observed. Neuronal firing was greatly suppressed following systemically administered uncompetitive NMDA antagonist (ketamine, 30 mg/kg, i.p.) with complete recovery by 4 h. After AGS kindling, LAMG neurons displayed a significantly increased incidence of onset-only patterns (93.3%, at 0.5 Hz), and mean acoustic responsiveness was also significantly increased (516.2% of control). LAMG neurons fired tonically during tonic convulsions and exhibited burst firing during post-tonic clonus. Greater acoustically-induced synchronization of LAMG firing, as indicated by elevated responsiveness and increased concentration of firing near the stimulus onset, may be critical for mediating the behavioral and EEG changes induced by AGS kindling. LAMG neuronal firing increases induced by AGS kindling may initiate these pathophysiological alterations, in part, by enhanced glutamate receptor-mediated excitation. This possibility is supported by the previously observed ability of an NMDA antagonist to reverse AGS kindling when focally microinjected into AMG, and the blockade of LAMG firing by administration of an uncompetitive NMDA antagonist observed in the present study.